Use of Compounds for the Preservation of the Human or Animal Body and Compositions Comprising Same

ABSTRACT

The present invention relates to the use of at least one compound of formula (I) R—(OCH 2 )n—OR′ in which R and R′, identical or different, represent a linear or branched alkyl radical comprising 1 to 5 carbon atoms and n is an index with a value comprised between 1 and 8, and/or at least one dialdehyde acetal type compound for the preservation of the human or animal body and/or the embalming of dead bodies. 
     It also relates to a composition comprising same and a process for preserving a human or animal body and/or embalming a dead body comprising the administration of the composition to the dead body in particular by injection, perfusion, immersion or topical application.

The present invention relates to the field of the preservation of humanor animal cadavers. More particularly, the invention relates to a noveluse, for non-therapeutic purposes, of at least one compound of the POM(PolyOxyMethylene dialkyl ether) type and/or of dialdehyde acetals forpreserving and/or embalming a human or animal body.

The embalming of a dead body is a practice requested by the families ofthe deceased in order to preserve an acceptable appearance for the bodyuntil its burial or cremation. However, under certain circumstances,this operation can become obligatory, in particular in the case ofinternational movements of the body, transport of the body beforecremation in coffins with walls thinner than those intended to beburied, or even in the absence of a coffin, in certain cases ofreturning home the bodies of individuals who have died in hospital, andalso in certain cases placing them in a temporary vault.

Moreover, the hygienic preservation of bodies the modern and effectivemeans of avoiding the propagation of diseases by the living coming intocontact with the dead, as well as pollution and soiling of objects andsurroundings.

Different compounds are known which are used for embalming and/orpreserving human or animal cadavers. In particular, phenol and aldehydessuch as formaldehyde and glutaraldehyde (1,5-pentanedial) are commonlyused in this field. However, these compounds are foul-smelling, highlytoxic and have a tendency to leave the treated body in a rigid state.

The French patent FR 1 457 037 discloses a composition for preservingdead animal bodies comprising δ-lactones which contain an additionaloxygen heteroatom in the nucleus. This composition can be applied to thecadaver by immersion, infusion or injection.

The American patent U.S. Pat. No. 5,827,511 describes a compositionwhich can be injected by arterial route, comprising glutaraldehyde, atleast one aromatic ether of ethanol, at least one hydrating agent suchas ethylene glycol and at least one alcohol.

The patent EP 1 127 490 describes a composition comprising at leastglycerol and, as active ingredient, an aqueous-alcoholic propolisextract. This composition can be painted onto the cadaver or injected byarterial route.

The patent WO2004/093541 discloses an injectable composition comprisingethanedial, also called glyoxal, and an aprotic polar solvent such asDMSO (dimethylsulphoxide) in aqueous solution.

Finally, the patent RU 2 116 725 describes a solution based ondiethylacetal (or 1,1-diethoxyethane) for embalming bodies.

However, the need still exists for novel products which make it possibleto avoid rigidity, pallor, emanations of odours and/or dehydration ofthe body while having low toxicity for the embalmer and a low cost.

The Applicant has now discovered that it is possible to use at least onecompound of the PolyOxymethylene dialkyl ether (POM) type and/ordialdehyde acetals for preserving and/or embalming a human or animalbody and thus to remedy one or more of the abovementioned drawbacks.

The POM compounds are known but for different uses. For example, theFrench patent FR 2 881 750 describes a use of POMs as fuels for fuelcells.

Similarly, dialdehyde acetal compounds are known but, for example, forbeing used as useful building blocks for organic synthesis (WO02/42524), as additives (EP0855436), or as adhesives (FR2844802) such asin particular 1,1,2,2-tetraethoxyethane.

The invention relates more particularly to the use of at least onecompound of formula (I) R—(OCH₂)_(n)—OR′ wherein R and R′, identical ordifferent, represent a linear or branched alkyl radical comprising 1 to5 carbon atoms and n is an index with a value comprised between 1 and 8,and/or at least one dialdehyde acetal of formula (II):

where R₂, R₃, R₄ and R₅ designate independently a linear or branchedalkyl radical comprising 1 to 8 carbon atoms, or R₂ and R₅ and/or R₃ andR₄ form together and with the two oxygen atoms to which they areattached a saturated or unsaturated heterocycle with 5 or 6 membersoptionally substituted by one or more groups chosen from OH, CH₂OH or alinear or branched alkyl radical comprising 1 to 8 carbon atoms; and R₁represents a CH—R₆—CH group where R₆ forms a bond or represents a linearor branched alkylene radical, comprising 1 to 5 carbon atoms or asaturated or unsaturated carbocycle comprising 3 to 8 carbon atoms; orR₁ is a saturated or unsaturated carbocycle comprising 3 to 8 carbonatoms.

Within the context of this description, the term “comprised between”must be interpreted as including the indicated limits.

Within the meaning of the invention, by “preserving” is meant the factthat the enzymatic action is stopped or slowed down in human or tissueanimal, compared with untreated tissue, which prevents or slows down theauto-catalytic destruction of this tissue, and/or that the tissuesresist outside attacks from bacteria and mycetes better than untreatedtissues.

The compounds (I) used according to the invention are PolyOxyMethylenedialkyl ethers which are designated by the initials POM forPolyOxyMethylene to which one or two letters are added (POMXX) making itpossible to identify the alkyl radicals(s) R and R′, M for methyl, E forethyl, P or i-P for (iso)propyl, B for butyl, Pe for pentyl and H forhexyl, as well as by an index corresponding to the number n of (CH₂O)units (POMXX_(n)).

These products are for example designated:

-   -   POMM_(n) (polyoxymethylene dimethyl ether) when the alkyl is the        methyl group, CH₃—(OCH₂)_(n)—OCH₃,    -   POME_(n) (polyoxymethylene diethyl ether) when the alkyl is the        ethyl group,    -   POMP_(n) (polyoxymethylene dipropyl ether) when the alkyl is the        propyl group,    -   POMB_(n) (polyoxymethylenedibutylether) when the alkyl is the        butyl group.

POMM_(n) is the name given to the compound with n oxymethylene units(formaldehyde). Thus methylal (n=1), is called POMM₁, and butylal iscalled POMB₁. If a mixture of products originating from the samesynthesis is used, it is called for example POMM_(3-8/) for a mixturecontaining POMMs with n=3 to 8.

These POMs are dissymmetrical in the case where R is different from R¹.It is for example possible to have a POMME₂ which designates apolyoxymethylene methyl ethyl ether with two (CH₂O) units, i.e.CH₃—(OCH₂)₂—OC₂H₅.

The advantages of POMs are probably linked to their chemical naturewhich itself depends on their synthesis method, by which it is possibleto control the chain length. Generally, the boiling point of POMsincreases with the number of formaldehyde (CH₂O) units and with thealkyl chain length. On the other hand, the solubility in waterdiminishes with the (—CH₂O—)_(n) chain length and with the alkyl chainlength.

From the point of view of toxicity, methylal (POMMi), ethylal (POME₁)and butylal (POMB₁) are much less toxic than methanol and formaldehyde.

Another advantage of POMs is their low cost. In fact, the synthesis ofPOMs uses methanol and formaldehyde, itself produced from methanol.

The synthesis of POMs has been well known for a number of years.

In particular, J. F. Walker's book, “FORMALDEHYDE”, Robert E. KriegerPublishing Company, Huntington, N.Y., 3^(rd) Edition of 1975 is areference work on the subject. It is in fact possible to find in thisreference work a description of the synthesis processes on pages 167 etseq. on the one hand, and 264 et seq. on the other hand. These synthesisprocesses are based on an acid catalysis of the reaction of an alcohol(methanol or ethanol) or an acetal (methylal or ethylal), withformaldehyde or an equivalent compound. This type of synthesis is alsoillustrated in numerous patent documents such as U.S. Pat. No. 2,449,469or JP 47-40772.

Other synthesis methods based on a Lewis acid type catalysis have alsobeen described. There can be mentioned the patent document GB 1120524which describes the synthesis of stable polyoxymethylene diethers withLewis acid type ionic catalysts.

Mixed POMs, i.e. those corresponding to the general formulaR—(OCH₂)_(n)—OR′ with R different from R′ are obtained either by directsynthesis according to the processes referred to above, or bytransacetalization of two different symmetrical POMs (R═R′).

According to an advantageous embodiment, the invention relates to theuse of at least one compound chosen from CH₃—(OCH₂)—OCH₃,CH₃—(OCH₂)₂—OCH₃, CH₃—(OCH₂)₃—OCH₃, CH₃—(OCH₂)₄—OCH₃, CH₃—(OCH₂)₅—OCH₃,CH₃—(OCH₂)₆—OCH₃, CH₃—(OCH₂)₇—OCH₃, CH₃—(OCH₂)₈—OCH₃, C₂H₅—(OCH₂)—OC₂H₅,C₂H₅—(OCH₂)₂—OC₂H₅, C₂H₅—(OCH₂)₃—OC₂H₅, C₂H₅—(OCH₂)₄—OC₂H₅,C₂H₅—(OCH₂)₅—OC₂H₅, C₂H₅—(OCH₂)₆—OC₂H₅, C₂H₅—(OCH₂)₇—OC₂H₅,C₂H₅—(OCH₂)₈—OC₂H₅, C₄H₉—(OCH₂)—OC₄H₉, CH₃—(OCH₂)—OC₂H₅,1,1,2,2-tetraethoxyethane, 1,1,3,3-tetraethoxypropane,1,1,3,3-tetramethoxypropane, 1,4,9,12-tetraoxadispiro[4,2,4,2]tetradecane, and mixtures thereof and very preferentially fromCH₃—(OCH₂)—OCH₃, CH₃—(OCH₂)₂—OCH₃, C₂H₅—(OCH₂)—OC₂H₅, C₄H₉—(OCH₂)—OC₄H₉,1,1,2,2-tetraethoxyethane, 1,1,3,3-tetraethoxypropane,1,1,3,3-tetramethoxypropane,1,4,9,12-tetraoxadispiro[4,2,4,2]tetradecane, and mixtures thereof.

According to an advantageous embodiment, the invention relates to theuse of at least one compound of formula R—(OCH₂)_(n)—OR′ the structureof which is symmetrical (R═R′).

According to a preferred embodiment, the invention relates to the use ofa mixture of compounds of formula R—(OCH₂)_(n)—OR in which either Rrepresents a methyl and n ranges from 2 to 8, or R represents an ethyland n ranges from 1 to 8.

According to a still more preferred embodiment, the invention relates tothe use of at least one compound POMM₂₋₈ which is a mixture of compoundsof formula CH₃—(OCH₂)_(n)—OCH₃ with n comprised between 2 and 8, thecomposition of which is as follows:

n 2 3 4 5 6 7 8 % 25-50 20-40 10-25 5-10 2-5 <2 <1

More particularly, a preferred composition of a POMM₂₋₈ compound is asfollows:

N 2 3 4 5 6 7 8 % 44 32 14 6 2.5 1 <1

According to a yet more preferred embodiment, the invention relates tothe use of at least one POME₁₋₈ compound which is a mixture of compoundsof formula C₂H₅—(OCH₂)_(n)—OC₂H₅ with n comprised between 1 and 8, thecomposition of which is as follows:

n 1 2 3 4 5 6 7 8 % 58 26 10 4 1.5 <1 <1 <1As compounds of formula (II), there can be mentioned, for example, thediacetals of glyoxal (ethanedial), of propanedial, and of glutaraldehyde(pentanedial), in particular those named hereafter of formula:

the diacetals of malonaldehyde, the diacetals of succinaldehyde,

and also the cyclic diacetals of dialdehyde,

where R₇-R₁₆ represent independently H, OH, CH₂OH or a linear orbranched alkyl radical comprising 1 to 8 carbon atoms; and R₁ representsa CH—R₆—CH group where R₆ is defined as previously, such as for example:

The synthesis methods for the compounds (II) according to the inventionare well known. For example, the French Patent Application FR2844802indicates that diacetals can be obtained by reaction of dialdehydes suchas glyoxal, malonaldehyde, or glutaraldehyde with alcohols such as forexample monoalcohols such as methanol, ethanol, diols such asethyleneglycol, diethyleneglycol, 1,4-butanediol, neopentylglycol, orpolyols such as glycerol, penta-erythritol.

The present invention also relates to a composition comprising at leastone of said compounds of formula (I) and/or (II) and glycerol.

According to an advantageous embodiment, the composition comprises12-70% by volume of at least one compound of formula (I) and/or (II),10-15% by volume of glycerol, 15-75% by volume of at least one alcoholsuch as for example ethanol, propanol and isopropanol and 0-10% byvolume of at least one colouring agent such as for example sunset yellowFCF, titanium dioxide and zinc oxide and/or an aroma producer such as inparticular mint, coriander, thyme, lemon grass and grapefruit.

This composition can moreover contain various constituents such as anantiseptic agent, which is advantageously a soap; a humectant such asethylene glycol and a polyethylene glycol; and mixtures thereof.

Another subject of the invention relates to a process for preserving ahuman or animal body and/or embalming a dead body comprising theadministration to the body of a composition comprising at least onecompound of formula (I) and/or formula (II) in which R₁, R₂, R₃, R₄ andR₅ are as described previously.

Two advantages of the process according to the invention are therapidity of execution, i.e. that the speed of decoagulation issignificant, as well as the rapidity of care.

In a first advantageous embodiment, the composition is injected byintra-arterial route into the body.

Preferentially, the composition injected by arterial route is an aqueoussolution the concentration of which in compounds of formula (I) and/orin compounds of formula (II) ranges from 1 to 25% by weight. Still morepreferentially, the composition is injected pure into a cavity.

In a second advantageous embodiment, the composition is perfused intothe body.

In a third advantageous embodiment, the body is immersed in thecomposition.

In a fourth advantageous embodiment, the composition is applied to thebody by topical route.

These methods of administration are well known to a person skilled inthe art.

The examples which follow are given purely by way of illustration andare in no way limitative of the invention.

EXAMPLES Example 1

A composition comprising 600 ml of POMM, 200 ml of glycerol, 100 ml ofsaline solution, 80 ml of soap and 20 ml of colorant and vegetable oilis injected by intra-arterial route into the dead body of a pig.

Example 2

The dead body of a duck is painted with a composition comprising 600 mlof 1,1,2,2-tetraethoxyethane available from Acros Organics, 200 ml ofglycerol, 100 ml of saline solution, 80 ml of soap and 20 ml of colorantand of vegetable oil.

Example 3

Example 2 is reproduced, replacing 1,1,2,2-tetraethoxyethane with1,1,3,3-tetraethoxypropane (available from Acros Organics).

1,1,3,3-tetraethoxypropane (CAS RN 122-31-6), available from AcrosOrganics, has a boiling point of 220° C. and a flash point of 88° C.

Example 4

Example 2 is reproduced, replacing 1,1,2,2-tetraethoxyethane with1,1,3,3-tetramethoxypropane (available from Acros Organics).

1,1,3,3-tetramethoxypropane (CAS RN 102-52-3), available from AcrosOrganics, has a boiling point of 183° C. and a flash point of 60° C.

Example 5

The dead body of a duck is painted with a composition comprising 600 mlof 1,4,9,12-tetraoxadispiro[4,2,4,2]tetradecane (available fromMaybridge SCR), 200 ml of glycerol, 100 ml of saline solution, 80 ml ofsoap, and 20 ml of colorant and vegetable oil.

Example 6

A dilution of a preservation fluid which consists either of POMM₂₋₈, orof POME₁₋₈ is prepared, by mixing 800 ml of fluid with 800 ml of tepidwater.

The composition of the POMM₂₋₈ used is as follows:

n 2 3 4 5 6 7 8 % 44 32 14 6 2.5 1 <1The composition of the POMM₁₋₈ used is as follows:

n 1 2 3 4 5 6 7 8 % 58 26 10 4 1.5 <1 <1 <1The preservation fluid is injected into the dead bodies of men and womenof various ages, by electric injection. This injection is carried outusing an electric pump.The injection is followed by drainage to the outside.The operation lasts only 30 minutes, which is relatively rapid.

Observations are made on the following days (D+1 to D+5 depending on thecase).

All of the treatment and observation conditions are summarized in thefollowing table:

Age 60 years 60 years 70 years 67 years 54 years 70 years 75 years Sex FM F F M M F Physical examination Haematoma Jaundice HaematomaDiscolouration* Discolouration** Healthy body Healthy body Height (cm)170 175 170 165 180 180 160 Weight (kg) 100 60 80 60 85 80 60 ProductPOME1-8 POMM2-8 POMM2-8 POMM2-8 POMM2-8 POMM2-8 POMM2-8 Injectiontechnique Femoral Femoral Femoral Carotid Carotid Carotid Femoralcarotid Electric injection yes yes yes yes yes yes yes Drainage methodCardiac Cardiac Cardiac Venous cardiac Venous cardiac Cardiac Cardiac(jugular) (jugular) Quantity 8 7.5 7.5 8 8 5 5 injected (L)Concentration 3.8 3.8 3.8 5 5 5 5 (% weight in water) Volume in cavity(1) 0.5 0.5 0.5 0.4 0.3 0.3 0.3 Concentration 100 100 100 100 100 100100 (% weight) Quantity drained (1) 1.6 2 6 5 6.5 3 3 Observations D = 0Nothing to Nothing to D + 1, D + 2, D + 1, D + 3, D + 1, D + 2, D + 2D + 3 date of the report at report at D + 4, D + 5 D + 4, D + 5 D + 3 NoNo injection D + 2 D + 2, no Same findings: Same findings, Samefindings: no preservation preservation odour, no no odour, no nopreservation preservation problems problems change in traces of problemsproblems coloration dehydration or of the body putrefaction, no gas,appearance very good *death by gastric haemorrhage **very pronouncedcyanoses, acute nicotinism, under anticoagulant treatment

According to this table, it is noted that even several days after theinjection of the preservation fluid, no change in the appearance of thebody, no cadaverous odour, no trace of mould, and no discharge from theorifices of the face or the lower abdomen is observed.

In particular, the surface tissues are also extremely supple and thelips have remained fine. Moreover, the skin remains slightly tinted bythe fluid, without it being necessary to resort to makeup cream.

The compounds according to the invention thus make it possible to makethe body-embalming operation easy and rapid.

1. Use of at least one compound of formula (I) R—(OCH₂)_(n)—OR′ whereinR and R′, identical or different, represent a linear or branched alkylradical comprising 1 to 5 carbon atoms and n is an index with a valuecomprised between 1 and 8, and/or (II)

where R₂, R₃, R₄ and R₅ designate independently a linear or branchedalkyl radical comprising 1 to 8 carbon atoms, or R₂ and R₅ and/or R₃ andR₄ form together and with the two oxygen atoms to which they areattached a saturated or unsaturated heterocycle with 5 or 6 membersoptionally substituted by one or more groups chosen from OH, CH₂OH or alinear or branched alkyl radical comprising 1 to 8 carbon atoms; and R₁represents a CH—R₆—CH group where R₆ forms a bond or represents a linearor branched alkylene radical, comprising 1 to 5 carbon atoms or asaturated or unsaturated carbocycle comprising 3 to 8 carbon atoms; orR₁ is a saturated or unsaturated carbocycle comprising 3 to 8 carbonatoms, for the preservation of the human or animal body and/or embalmingof dead bodies.
 2. Use according to claim 1, characterized in that thecompound chosen from CH₃—(OCH₂)—OCH₃, CH₃—(OCH₂)₂−OCH₃,CH₃—(OCH₂)₃—OCH₃, CH₃—(OCH₂)₄—OCH₃, CH₃—(OCH₂)₅—OCH₃, CH₃—(OCH₂)₆—OCH₃,CH₃—(OCH₂)₇—OCH₃, CH₃—(OCH₂)₈—OCH₃, C₂H₅—(OCH₂)—OC₂H₅,C₂H₅—(OCH₂)₂—OC₂H₅, C₂H₅—(OCH₂)₃—OC₂H₅, C₂H₅—(OCH₂)₄—OC₂H₅,C₂H₅—(OCH₂)₅—OC₂H₅, C₂H₅—(OCH₂)₆—OC₂H₅, C₂H₅—(OCH₂)₇—OC₂H₅,C₂H₅—(OCH₂)₈—OC₂H₅C₄H₉—(OCH₂)—OC₄H₉, CH₃—(OCH₂)—OC₂H₅,1,1,2,2-tetraethoxyethane, 1,1,3,3-tetraethoxypropane,1,1,3,3-tetramethoxypropane,1,4,9,12-tetraoxadispiro[4,2,4,2]tetradecane, and mixtures thereof andvery preferentially from CH₃—(OCH₂)—OCH₃, CH₃—(OCH₂)₂—OCH₃,C₂H₅—(OCH₂)—OC₂H₅, C₄H₉—(OCH₂)—OC₄H₉, 1,1,2,2-tetraethoxyethane,1,1,3,3-tetraethoxypropane, 1,1,3,3-tetramethoxypropane,1,4,9,12-tetraoxadispiro[4,2,4,2]tetradecane, and mixtures thereof. 3.Use according to claim 1, characterized in that the compound of formula(I) is of symmetrical structure.
 4. Use according to claim 1,characterized in that the compound is POMM₂₋₈ which is a mixture ofcompounds of formula CH₃—(OCH₂)_(n)—OCH₃ with n comprised between 2 and8.
 5. Use according to claim 1, characterized in that the compound isPOME₁₋₈ which is a mixture of compounds of formula C₂H₅—(OCH₂)_(n)—OC₂H₅with n comprised between 1 and
 8. 6. Composition comprising at least oneof the compounds according to claim 1 and glycerol.
 7. Compositioncomprising 12-70% by volume of said compound according to claim 1,10-15% by volume of glycerol, 15-75% by volume of at least one alcoholand 0-10% by volume of at least one colouring agent and/or aromaproducer.
 8. Process for preserving a human or animal body and/orembalming a dead body comprising the administration to said body of acomposition comprising at least one compound according to claim
 1. 9.Process according to claim 8, characterized in that the composition isinjected into said body by intra-arterial route.
 10. Process accordingto claim 8, characterized in that the composition is perfused into saidbody.
 11. Process according to claim 8, characterized in that said bodyis immersed in the composition.
 12. Process according to claim 8,characterized in that the composition is applied to said body by topicalroute.
 13. Process for preserving a human or animal body and/orembalming a dead body comprising the administration to said body of acomposition comprising at least one compound according to claim
 1. 14.Process for preserving a human or animal body and/or embalming a deadbody comprising the administration to said body of a compositioncomprising at least one compound according to claim
 2. 15. Process forpreserving a human or animal body and/or embalming a dead bodycomprising the administration to said body of a composition comprisingat least one compound according to claim
 3. 16. Process for preserving ahuman or animal body and/or embalming a dead body comprising theadministration to said body of a composition comprising at least onecompound according to claim
 4. 17. Process for preserving a human oranimal body and/or embalming a dead body comprising the administrationto said body of a composition comprising at least one compound accordingto claim
 5. 18. Composition comprising at least one of the compoundsaccording to claim 2 and glycerol.
 19. Composition comprising 12-70% byvolume of said compound according to claim 2, 10-15% by volume ofglycerol, 15-75% by volume of at least one alcohol and 0-10% by volumeof at least one colouring agent and/or aroma producer.
 20. Compositioncomprising 12-70% by volume of said compound according to claim 3,10-15% by volume of glycerol, 15-75% by volume of at least one alcoholand 0-10% by volume of at least one colouring agent and/or aromaproducer.
 21. Composition comprising 12-70% by volume of said compoundaccording to claim 4, 10-15% by volume of glycerol, 15-75% by volume ofat least one alcohol and 0-10% by volume of at least one colouring agentand/or aroma producer.
 22. Composition comprising 12-70% by volume ofsaid compound according to claim 5, 10-15% by volume of glycerol, 15-75%by volume of at least one alcohol and 0-10% by volume of at least onecolouring agent and/or aroma producer.